目的经受体大鼠门静脉途径输注供体大鼠的骨髓细胞,观察受体大鼠小肠移植排斥反应状况及生存时间,并分析其细胞因子的改变与病理学改变之间的关系。方法取雄性BN大鼠30只为供体、雌性Lewis大鼠30只为受体建立异位节段小肠移植模型,随机分为3组:BN-Lewis组(对照组)、BN-Lewis+FK506组(FK506组)、BN-Lewis+BM(P.V.injection)+FK506组(PV组);对各组作生存时间分析,并于术后7、14、30、60和90 d制作移植小肠的病理切片评估排斥反应程度;分别于术后7、14、21、30 d留取受体血清,ELISA法测定血清中IL-2、IL-10水平。结果与对照组、FK506组相比,PV组受体大鼠存活时间明显延长(P〈0.01);对照组大鼠术后第14天即已出现严重的急性排斥反应,而FK506组急性排斥反应发生时间延迟至第30天;PV组在术后30 d之内均未见严重的急性排斥反应。各组移植后受体IL-2浓度均增加,但PV组的IL-2增高幅度明显低于对照组和FK506组(P〈0.01);移植后受体大鼠血清IL-10浓度也均增加,但PV组IL-10升高幅度大于对照组和FK506组(P〈0.01)。结论骨髓细胞经门静脉输注能明显延长小肠移植物的生存时间,外周血清IL-2、IL-10浓度变化与排斥反应相关。
Objective To observe the acute rejection and survival time following small bowel transplantation(SBT) in the rat model,and determine the relationship between changes in serum cytokine levels and histopathology.Methods BN and Lewis rats were used as donors(n=30) and recipients(n=30) respectively.Lewis rats were assigned randomly to three groups according to the different immunosuppressive regimens:untreated Lewis rats receiving a BN bowel graft,untreated control group(n=10);recipients fed on 1 mg/kg FK506 daily from day 0 to 5(FK506 group,n=10);recipients subjected to donor-derived bone marrow cells infusion via portal vein(DSBMI-PV) intraoperatively(day 0) and daily feed of 1 mg/kg FK506 from day 0 to 5(PV group,n=10).The survival time of all groups was recorded,and histopathologic changes of the small bowel graft were examined on the day 7,14,30,60 and 90.The levels of serum IL-2 and IL-10 in recipients were measured by enzyme labeled immunosorbent assay(ELISA) kit on the day 7,14,21,30.Results The mean survival time(MST) in PV group was significantly longer than in control group and FK506 group(P0.01).Signs of acute rejection were revealed in control group and FK506 group by histopathologic examination of intestinal grafts on the post-transplant day 14 and 30,respectively.As compared with control group and FK506 group,allografts treated with DSBMI-PV-FK506 showed no obvious signs of rejection within 30 days after SBT.The serum IL-2 level in all recipients was increased post-transplant.The IL-2 level in PV group was lower than that in control group and FK506(P0.01).On the contrary,the IL-10 level in PV group was higher than that in control group and FK506 group(P0.01).Conclusion Administration of bone marrow cells via portal vein prolonged significantly the survival of the small bowel graft.Serum levels of IL-2 and IL-10 were related with acute rejection.